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A primate virus generates transformed human cells by fusion.

Duelli DM, Hearn S, Myers MP, Lazebnik Y - J. Cell Biol. (2005)

Bottom Line: Amodel that explains both the origin and sporadic nature of cancer argues that cancer cells are a chance result of events that cause genomic and epigenetic variability.We also show that this virus can produce viable oncogenically transformed cells by fusing cells that are otherwise destined to die.Therefore, we argue that viruses can contribute to carcinogenesis by fusing cells.

View Article: PubMed Central - PubMed

Affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

ABSTRACT
Amodel that explains both the origin and sporadic nature of cancer argues that cancer cells are a chance result of events that cause genomic and epigenetic variability. The prevailing view is that these events are mutations that affect chromosome segregation or stability. However, genomic and epigenetic variability is also triggered by cell fusion, which is often caused by viruses. Yet, cells fused by viruses are considered harmless because they die. We provide evidence that a primate virus uses both viral and exosomal proteins involved in cell fusion to produce transformed proliferating human cells. Although normal cells indeed fail to proliferate after fusion, expression of an oncogene or a mutated tumor suppressor p53 in just one of the fusion partners is sufficient to produce heterogeneous progeny. We also show that this virus can produce viable oncogenically transformed cells by fusing cells that are otherwise destined to die. Therefore, we argue that viruses can contribute to carcinogenesis by fusing cells.

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Related in: MedlinePlus

Expression of E1A or suppression of p53 is sufficient for proliferation of hybrids induced by MPMVE. (A) Detroit 551 cells resistant to puromycin (D0P), hygromycin (D0H), transduced with E1A and resistant to hygromycin (DEH), or transduced with p53 R175H and resistant to hygromycin (Dp53R175HH) were cultured for 16 h in combinations as indicated with or without MPMVE and then for an additional 20 d in fresh medium containing hygromycin and puromycin. The cells were then visualized by staining with crystal violet. (B) Cell colonies from various fields of the bottom right plate in A. Note the diversity in cell morphology among the fields. The data are from one out of three experiments, all of which produced similar results. Bars, 200 μm.
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fig7: Expression of E1A or suppression of p53 is sufficient for proliferation of hybrids induced by MPMVE. (A) Detroit 551 cells resistant to puromycin (D0P), hygromycin (D0H), transduced with E1A and resistant to hygromycin (DEH), or transduced with p53 R175H and resistant to hygromycin (Dp53R175HH) were cultured for 16 h in combinations as indicated with or without MPMVE and then for an additional 20 d in fresh medium containing hygromycin and puromycin. The cells were then visualized by staining with crystal violet. (B) Cell colonies from various fields of the bottom right plate in A. Note the diversity in cell morphology among the fields. The data are from one out of three experiments, all of which produced similar results. Bars, 200 μm.

Mentions: Because our observations contrasted with the view that cells fused by active viruses do not proliferate, we investigated what is required to make hybrids proliferate. None of the normal primary cell lines that we tested, which included human fibroblasts I0, HSF43, SF68, BJ, WI38, and Detroit 551; human umbilical vein endothelial cells; and renal proximal epithelial tubule cells, produced colonies or mononuclear cells after fusion by MPMVE (Fig. 7 A, left, and not depicted). Therefore, we concluded that these cells not only failed to proliferate but did not undergo even a single cell division after fusion. The cells were dikaryons, with occasional polykaryons, and remained attached for at least 20 d and appeared healthy (Fig. S2 C). Therefore, cell fusion was cytostatic but not cytotoxic to normal cells. Hence, we concluded that fusion of normal differentiated cells by MPMVE is unlikely to result in proliferating progeny.


A primate virus generates transformed human cells by fusion.

Duelli DM, Hearn S, Myers MP, Lazebnik Y - J. Cell Biol. (2005)

Expression of E1A or suppression of p53 is sufficient for proliferation of hybrids induced by MPMVE. (A) Detroit 551 cells resistant to puromycin (D0P), hygromycin (D0H), transduced with E1A and resistant to hygromycin (DEH), or transduced with p53 R175H and resistant to hygromycin (Dp53R175HH) were cultured for 16 h in combinations as indicated with or without MPMVE and then for an additional 20 d in fresh medium containing hygromycin and puromycin. The cells were then visualized by staining with crystal violet. (B) Cell colonies from various fields of the bottom right plate in A. Note the diversity in cell morphology among the fields. The data are from one out of three experiments, all of which produced similar results. Bars, 200 μm.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2171256&req=5

fig7: Expression of E1A or suppression of p53 is sufficient for proliferation of hybrids induced by MPMVE. (A) Detroit 551 cells resistant to puromycin (D0P), hygromycin (D0H), transduced with E1A and resistant to hygromycin (DEH), or transduced with p53 R175H and resistant to hygromycin (Dp53R175HH) were cultured for 16 h in combinations as indicated with or without MPMVE and then for an additional 20 d in fresh medium containing hygromycin and puromycin. The cells were then visualized by staining with crystal violet. (B) Cell colonies from various fields of the bottom right plate in A. Note the diversity in cell morphology among the fields. The data are from one out of three experiments, all of which produced similar results. Bars, 200 μm.
Mentions: Because our observations contrasted with the view that cells fused by active viruses do not proliferate, we investigated what is required to make hybrids proliferate. None of the normal primary cell lines that we tested, which included human fibroblasts I0, HSF43, SF68, BJ, WI38, and Detroit 551; human umbilical vein endothelial cells; and renal proximal epithelial tubule cells, produced colonies or mononuclear cells after fusion by MPMVE (Fig. 7 A, left, and not depicted). Therefore, we concluded that these cells not only failed to proliferate but did not undergo even a single cell division after fusion. The cells were dikaryons, with occasional polykaryons, and remained attached for at least 20 d and appeared healthy (Fig. S2 C). Therefore, cell fusion was cytostatic but not cytotoxic to normal cells. Hence, we concluded that fusion of normal differentiated cells by MPMVE is unlikely to result in proliferating progeny.

Bottom Line: Amodel that explains both the origin and sporadic nature of cancer argues that cancer cells are a chance result of events that cause genomic and epigenetic variability.We also show that this virus can produce viable oncogenically transformed cells by fusing cells that are otherwise destined to die.Therefore, we argue that viruses can contribute to carcinogenesis by fusing cells.

View Article: PubMed Central - PubMed

Affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

ABSTRACT
Amodel that explains both the origin and sporadic nature of cancer argues that cancer cells are a chance result of events that cause genomic and epigenetic variability. The prevailing view is that these events are mutations that affect chromosome segregation or stability. However, genomic and epigenetic variability is also triggered by cell fusion, which is often caused by viruses. Yet, cells fused by viruses are considered harmless because they die. We provide evidence that a primate virus uses both viral and exosomal proteins involved in cell fusion to produce transformed proliferating human cells. Although normal cells indeed fail to proliferate after fusion, expression of an oncogene or a mutated tumor suppressor p53 in just one of the fusion partners is sufficient to produce heterogeneous progeny. We also show that this virus can produce viable oncogenically transformed cells by fusing cells that are otherwise destined to die. Therefore, we argue that viruses can contribute to carcinogenesis by fusing cells.

Show MeSH
Related in: MedlinePlus